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Myostatin regulates the production of fibroblast growth factor 23 (FGF23) in UMR106 osteoblast–like cells

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Title: Myostatin regulates the production of fibroblast growth factor 23 (FGF23) in UMR106 osteoblast–like cells
Authors: Franz Ewendt, Martina Feger, Michael Föller
Source: Pflugers Arch
Publisher Information: Springer Science and Business Media LLC, 2021.
Publication Year: 2021
Subject Terms: 0301 basic medicine, Signaling and Cell Physiology, Pyridines, Activin Receptors, Dioxoles, p38 Mitogen-Activated Protein Kinases, Cell Line, Mice, 03 medical and health sciences, Cell Line, Tumor [MeSH], Activin Receptors/metabolism [MeSH], Cell Line [MeSH], Fibroblast Growth Factor-23/genetics [MeSH], Osteoblasts/metabolism [MeSH], Signaling and cell physiology, Withanolides/pharmacology [MeSH], TGF-β, Phosphate, p38 Mitogen-Activated Protein Kinases/antagonists, Vitamin D, Imidazoles/pharmacology [MeSH], Benzamides/pharmacology [MeSH], Pyridines/pharmacology [MeSH], Calcium/metabolism [MeSH], Protein Kinase Inhibitors/pharmacology [MeSH], NF-kappa B/antagonists, Fibroblast Growth Factor-23/metabolism [MeSH], Rats [MeSH], Animals [MeSH], Mice [MeSH], NF-kappa B/metabolism [MeSH], Ca, Myostatin/pharmacology [MeSH], p38 Mitogen-Activated Protein Kinases/metabolism [MeSH], p38MAPK, Dioxoles/pharmacology [MeSH], Osteoblasts/drug effects [MeSH], Cell Line, Tumor, Animals, Protein Kinase Inhibitors, Withanolides, 0303 health sciences, Osteoblasts, Imidazoles, NF-kappa B, Myostatin, Rats, Fibroblast Growth Factor-23, Benzamides, Calcium, ddc:570
Description: Myostatin is a signaling molecule produced by skeletal muscle cells (myokine) that inhibits muscle hypertrophy and has further paracrine and endocrine effects in other organs including bone. Myostatin binds to activin receptor type 2B which forms a complex with transforming growth factor-β type I receptor (TGF-βRI) and induces intracellular p38MAPK and NFκB signaling. Fibroblast growth factor 23 (FGF23) is a paracrine and endocrine mediator produced by bone cells and regulates phosphate and vitamin D metabolism in the kidney. P38MAPK and NFκB-dependent store-operated Ca2+ entry (SOCE) are positive regulators of FGF23 production. Here, we explored whether myostatin influences the synthesis of FGF23. Fgf23 gene expression was determined by qRT-PCR and FGF23 protein by ELISA in UMR106 osteoblast–like cells. UMR106 cells expressed activin receptor type 2A and B. Myostatin upregulated Fgf23 gene expression and protein production. The myostatin effect on Fgf23 was significantly attenuated by TGF-βRI inhibitor SB431542, p38MAPK inhibitor SB202190, and NFκB inhibitor withaferin A. Moreover, SOCE inhibitor 2-APB blunted the myostatin effect on Fgf23. Taken together, myostatin is a stimulator of Fgf23 expression in UMR106 cells, an effect at least partially mediated by downstream TGF-βRI/p38MAPK signaling as well as NFκB-dependent SOCE.
Document Type: Article
Other literature type
File Description: 1 Online-Ressource; application/pdf
Language: English
ISSN: 1432-2013
0031-6768
DOI: 10.1007/s00424-021-02561-y
DOI: 10.25673/110730
Access URL: https://link.springer.com/content/pdf/10.1007/s00424-021-02561-y.pdf
https://pubmed.ncbi.nlm.nih.gov/33895875
https://link.springer.com/content/pdf/10.1007/s00424-021-02561-y.pdf
https://www.ncbi.nlm.nih.gov/pubmed/33895875
https://link.springer.com/article/10.1007/s00424-021-02561-y
https://pubmed.ncbi.nlm.nih.gov/33895875/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8164604
https://europepmc.org/article/MED/33895875
https://repository.publisso.de/resource/frl:6446960
Rights: CC BY
URL: http://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (http://creativecommons.org/licenses/by/4.0/) .
Accession Number: edsair.doi.dedup.....9b9e18805ed1ea5ec4efa1377ce6b565
Database: OpenAIRE
Description
Abstract:Myostatin is a signaling molecule produced by skeletal muscle cells (myokine) that inhibits muscle hypertrophy and has further paracrine and endocrine effects in other organs including bone. Myostatin binds to activin receptor type 2B which forms a complex with transforming growth factor-β type I receptor (TGF-βRI) and induces intracellular p38MAPK and NFκB signaling. Fibroblast growth factor 23 (FGF23) is a paracrine and endocrine mediator produced by bone cells and regulates phosphate and vitamin D metabolism in the kidney. P38MAPK and NFκB-dependent store-operated Ca2+ entry (SOCE) are positive regulators of FGF23 production. Here, we explored whether myostatin influences the synthesis of FGF23. Fgf23 gene expression was determined by qRT-PCR and FGF23 protein by ELISA in UMR106 osteoblast–like cells. UMR106 cells expressed activin receptor type 2A and B. Myostatin upregulated Fgf23 gene expression and protein production. The myostatin effect on Fgf23 was significantly attenuated by TGF-βRI inhibitor SB431542, p38MAPK inhibitor SB202190, and NFκB inhibitor withaferin A. Moreover, SOCE inhibitor 2-APB blunted the myostatin effect on Fgf23. Taken together, myostatin is a stimulator of Fgf23 expression in UMR106 cells, an effect at least partially mediated by downstream TGF-βRI/p38MAPK signaling as well as NFκB-dependent SOCE.
ISSN:14322013
00316768
DOI:10.1007/s00424-021-02561-y